The long term objectives of this proposal will be to develop improved chemical syntheses for biologically active natural products and their structural analogs. These syntheses are destined to rely on conceptually novel radical annulation procedures. The prostaglandins PGF2-Alpha and prostacyclin as well as the carbocyclic analog methano-PGI, are the preeminent bioactive substances which are targeted for synthesis in this proposal. Prostaglandin PGF2-Alpha exhibits a diverse spectrum of physiological activbities the most noteworthy of these are: a) potent arteriolar constrictor activity, b) uterine leutolytic activity in animals, c) a powerful oxytocic effect which has been exploited for pregnancy interruption, and d) the propensity to increase the ability of sperm to penetrate cervical mucus. Prostacyclin (PGI) has been shown to be an exceptionally potent inhibitor of platelet aggregation and also a powerful vasodialator. during the course of an investigation into the design of hydrolytically stable analogs of PGI, the carbocyclic derivative 9(0)-methano-Delta 6 (9 Alpha)-PGI, was recently synthesized. This substance has been shown to be considerably more active than the known analog carbocyclin. Methano-PGI is one-tenth as active as prostacyclin in inhibiting platelet aggregation induced by ADP in rabbit platelet rich plasma. It has also been demonstrated equipotent to PGE2 in its cytoprotective action rabbit stomach epithelial cells. In addition, synthetic approaches to the alkaloids Alpha- dihydroerthyramine as well as the cyclopentanoid antibiotic coriolin are proposed which will rely on "homolytically accelerated" 5-endo-trig radical cyclizations. The new radical annulation procedures described in this proposal are distinguished by being non-reductive in nature. The characteristic is predicted to facilitate the strategic introduction of functionality into organic molecules. Moreover, the non-reductive termination of radical reactions should result in the ability to exploit otherwise "disfavored" modes of ring closure.